Effects of high glucose and TGF-β1 on the expression of collagen IV and vascular endothelial growth factor in mouse podocytes

Cruz, M. Carmen Iglesias-de la; Ziyadeh, Fuad N.; Isono, Motohide; Kouahou, M.; Han, Dong Cheol; Kalluri, Raghu; Mündel, Peter; Chen, Sheldon

doi:10.1046/j.1523-1755.2002.00528.x

Cited by 188 publications

(182 citation statements)

References 55 publications

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“…Using IHC analysis, we found variable IGF-IR levels in clinical specimens of hepatic metastases that did not always correlate with collagen IV levels (data not shown). Although the regulation of collagen IV gene expression is not yet fully understood (Khoshnoodi et al, 2008), several factors have been identified, including high glucose levels, transforming growth factor-b1 (Iglesias-de la Cruz et al, 2002), hypoxia via the hypoxia-inducible factor (HIF)-1a (Steenhard et al, 2010) and the tumor-suppressor von Hippel-Lindau that in addition to its role in regulating HIF-1a levels was also implicated in the assembly of collagen IV matrix (Kurban et al, 2008). Some of these factors have also been shown to play important roles during the early stages of liver metastasis (VidalVanaclocha, 2008).…”

Section: Lung Metastasismentioning

confidence: 99%

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

et al. 2011

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The liver is a major site of metastasis for human malignancies, yet the factors that regulate tumor cell survival and growth in this organ remain elusive. Previously, we reported that M-27 IGFÀIR murine lung carcinoma cells with ectopic insulin-like growth factor-1 (IGF-I) receptor overexpression acquired a site-specific, liver-metastasizing potential. Gene expression profiling and subsequent RNA and protein analyses revealed that this was associated with major changes to the expression of extracellular matrix (ECM) protein-encoding genes including type III, IV and XVIII collagen genes, and these changes were also observed in the respective tumors in vivo. Because type IV collagen was the most prominently altered ECM protein in this model, we further analyzed its functional relevance to liver metastasis. M-27 cells stably overexpressing type IV collagen a1 and a2 chains were generated and their growth and metastatic properties investigated. We found that these cells acquired a site-selective growth advantage in the liver and this was associated with cell rescue from anoikis in a collagen IV/a2 integrin/FAK-dependent manner and increased responsiveness to IGF-I. Conversely, collagen IV or focal adhesion kinase (FAK) silencing by smallinterfering RNA in highly metastatic tumor cells enhanced anoikis and decreased liver metastases formation. Moreover, analysis of human surgical specimens revealed uniformly high collagen IV expression in 65/65 hepatic metastases analyzed, regardless of tissue of origin, whereas it was variable and generally low in 50/50 primary colorectal carcinoma specimens examined. The results suggest that collagen IV-conveyed signals are essential cues for liver metastasis in diverse tumor types and identify mediators of collagen IV signaling as potential therapeutic targets in the management of hepatic metastases.

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Section: Lung Metastasismentioning

confidence: 99%

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

et al. 2011

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“…Cells of passages 6 to 10 were used in the experiments. An immortalized mouse podocyte cell line was a gift from Dr. Peter Mundel (Albert Einstein College of Medicine, Bronx, NY) and maintained as documented previously (32). After reaching 80% confluence, cells were exposed to 0.5% FBS for 12 h followed by the treatment with desired reagents.…”

Section: Cell Culturementioning

confidence: 99%

Therapeutic Potential of Angiostatin in Diabetic Nephropathy

Zhang¹,

Wang²,

Lu³

et al. 2006

Journal of the American Society of Nephrology

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Angiostatin is a proteolytic fragment of plasminogen and a potent angiogenic inhibitor. Previous studies have shown that angiostatin inhibits retinal neovascularization and reduces retinal vascular permeability in diabetic retinopathy. Here, it is reported for the first time that angiostatin is also implicated in diabetic nephropathy (DN). Angiostatin levels are dramatically decreased in the kidney of streptozotocin-induced diabetic rats. Consistently, diabetic kidneys also showed decreased expression and proteolytic activities of matrix metalloproteinase-2, an enzyme that releases angiostatin from plasminogen. Adenovirus-mediated delivery of angiostatin significantly alleviated albuminuria and attenuated the glomerular hypertrophy in diabetic rats. Moreover, angiostatin treatment downregulated the expression of vascular endothelial growth factor and TGF-␤1, two major pathogenic factors of DN, in diabetic kidneys. In cultured human mesangial cells, angiostatin blocked the overexpression of vascular endothelial growth factor and TGF-␤1 that were induced by high glucose while increasing the levels of pigment epithelium-derived factor, an endogenous inhibitor of DN. Moreover, angiostatin effectively inhibited the high-glucose-and TGF-␤1-induced overproduction of proinflammatory factors and extracellular matrix proteins via blockade of the Smad signaling pathway. These findings suggest that the decrease of angiostatin levels in diabetic kidney may contribute to the pathologic changes such as inflammation and fibrosis in DN. Therefore, angiostatin has therapeutic potential in DN as a result of its anti-inflammatory and antifibrosis activities.

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“…Because collagen is proline rich, incorporation of proline was used as an additional relative estimate of collagen production (16). Confluent CF in 96-well plates were exposed to 1 and 3 M pioglitazone for 72 h. A total of 1 Ci of l[2,3,4,5- …”

Section: [ 3 H]proline Incorporationmentioning

confidence: 99%

Pioglitazone Inhibits Cell Growth and Reduces Matrix Production in Human Kidney Fibroblasts

Zafiriou¹,

Stanners²,

Saad³

et al. 2005

Journal of the American Society of Nephrology

104

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Peroxisome proliferator-activated receptor-␥ (PPAR-␥) agonists are increasingly used in patients with diabetes, and small studies have suggested a beneficial effect on renal function, but their effects on extracellular matrix (ECM) turnover are unknown. The aims of this study were to investigate the effects of the PPAR-␥ agonist pioglitazone on growth and matrix production in human cortical fibroblasts (CF). Cell growth and ECM production and turnover were measured in human CF in the presence and absence of 1 and 3 M pioglitazone. Exposure of CF to pioglitazone caused an antiproliferative (P < 0.0001) and hypertrophic (P < 0.0001) effect; reduced type IV collagen secretion (P < 0.01), fibronectin secretion (P < 0.0001), and proline incorporation (P < 0.0001); decreased MMP-9 activity (P < 0.05); and reduced tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 secretion (P < 0.001 and P < 0.0001, respectively). These effects were independent of TGF-␤1. A reduction in ECM production was similarly observed when CF were exposed to a selective PPAR-␥ agonist (L-805645) in concentrations that caused no toxicity, confirming the antifibrotic effects of pioglitazone were mediated through a PPAR-␥-dependent mechanism. Exposure of CF to high glucose conditions induced an increase in the expression of collagen IV (P < 0.05), which was reversed both in the presence of pioglitazone (1 and 3 M) and by L-805645. In summary, exposure of human CF to pioglitazone causes an antiproliferative effect and reduces ECM production through mechanisms that include reducing TIMP activity, independent of TGF-␤1. These studies suggest that the PPAR-␥ agonists may have a specific role in ameliorating the course of progressive tubulointerstitial fibrosis under both normoglycemic and hyperglycemic states.

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Effects of high glucose and TGF-β1 on the expression of collagen IV and vascular endothelial growth factor in mouse podocytes

Cited by 188 publications

References 55 publications

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

Therapeutic Potential of Angiostatin in Diabetic Nephropathy

Pioglitazone Inhibits Cell Growth and Reduces Matrix Production in Human Kidney Fibroblasts

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